Topical GDF11 accelerates skin wound healing in both type 1 and 2 diabetic mouse models

Li, Qingqi; Jiao, Lei; Shao, Yingchun; Li, Mengmeng; Gong, Manyu; Zhang, Yuanyuan; Tan, Zhongyue; Wang, Yanying; Yang, Xuewen; Wang, Zhiguo; Zhang, Ying

doi:10.1016/j.bbrc.2020.05.036

Cited by 14 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M1 macrophages are mainly involved in initiating and maintaining an inflammatory response, and M2 macrophages are mainly involved in inflammation regression [10,[34][35] . Our previous study has identified that GDF11 could accelerate the healing of diabetic wounds [17] . In another study by our team, we found that GDF11 protected cardiomyocytes from hypoxia-mediated apoptosis by regulating autophagy [36] .…”

Section: Manipulations That Promote Phenotypic Transformation Ofmentioning

confidence: 97%

See 1 more Smart Citation

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Gong

Yang

Wang

et al. 2023

Frigid Zone Medicine

Self Cite

View full text Add to dashboard Cite

Background Myocardial infarctions (MI) is a major threat to human health especially in people exposed to cold environment. The polarization of macrophages towards different functional phenotypes (M1 macrophages and M2 macrophages) is closely related to MI repairment. The growth differentiation factor 11 (GDF11) has been reported to play a momentous role in inflammatory associated diseases. In this study, we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI. Methods In vivo, the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery (LAD), and mice were randomly divided into the sham group, MI group, and MI+GDF11 group. The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography, triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue. In vitro, based on the RAW264.7 cell line, the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR, Western blot, and flow cytometry. Results We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice. And GDF11 supplementation can improve the cardiac function. Moreover, GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice. Furthermore, the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance. At the cellular level, application of GDF11 could inhibit the expression of M1 macrophage (classically activated macrophage) markers iNOS, interleukin (IL)-1β, and IL-6 in a dose-dependent manner. In contrast, GDF11 significantly increased the level of M2 macrophage markers including IL-10, CD206, arginase 1 (Arg1), and vascular endothelial growth factor (VEGF). Interestingly, GDF11 could promote M1 macrophages polarizing to M2 macrophages. At the molecular level, GDF11 significantly down-regulated the Notch1 signaling pathway, the activation of which has been demonstrated to promote M1 polarization in macrophages. Conclusions GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

show abstract

Section: Manipulations That Promote Phenotypic Transformation Ofmentioning

confidence: 97%

“…Our previous study had shown that GDF11 could significantly inhibit the level of inflammatory factors at the wound area during the healing process of diabetic wounds [17] . In this process, macrophage-specific polarization may be involved in the healing process of diabetic wounds.…”

mentioning

confidence: 94%

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Gong

Yang

Wang

et al. 2023

Frigid Zone Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, if diabetic wounds are poorly treated, dry skin and callus formation can lead to further wound deterioration and the formation of foot ulcers, neuropathy, and structural deformity, which greatly affect the physical and mental health of patients. 5,6 Skin is the largest organ of the human body and is composed of epidermal, dermal, and subcutaneous tissues, 7,8 as well as a large number of peripheral nerve fibers for distinguishing pain, temperature, and other sensations. 9 Diabetic patients can suffer peripheral nerve system damage, with significantly lower nerve distribution and axonal plasticity than found in normal tissue.…”

Section: Introductionmentioning

confidence: 99%

“…The regeneration of peripheral nerves after skin wound healing and the recovery of sensory function on this basis are essential for high‐quality wound repair. Furthermore, if diabetic wounds are poorly treated, dry skin and callus formation can lead to further wound deterioration and the formation of foot ulcers, neuropathy, and structural deformity, which greatly affect the physical and mental health of patients 5,6 …”

Section: Introductionmentioning

confidence: 99%

Peptide RL‐QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds

Wang

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post‐traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL‐QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full‐thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL‐QN15 treatment. Furthermore, RL‐QN15 promoted the proliferation, migration, and axonal length of neuron‐like PC12 cells, which was likely associated with activation of the phosphatidylinositol‐3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL‐QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL‐QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL‐QN15 peptide‐based therapeutics against diabetic skin wounds.

show abstract

“…YAP interacts with Smad2/3 through TGF-β, leading to the accumulation of phosphorylated Smad2/3 and promoting tissue repair24 (Figure2). In a cellular model of wound healing, HaCaT cell migration was decreased by YAP inhibition17 ; and in mouse models of type I and II diabetes, overexpression of growth differentiation factor 11 (GDF11) stimulated dermal fibrosis and accelerated skin wound closure via YAP/Smad2/3/CTGF signaling 25. Nuclear localization of YAP was shown to be increased by treatment with calcipotriol, which induced EMT through the YAP/TGF-β/Smad pathway to Mechanism of Yes-associated protein (YAP)/transforming growth factor beta 1 (TGF-β1)/Smad regulation in wound healing.…”

mentioning

confidence: 99%

Recent advances in the role of Yes‐associated protein in dermatosis

Jia

Liu

2023

Skin Research and Technology

View full text Add to dashboard Cite

Background: Dermatosis is a general term for diseases of the skin and skin appendages including scleroderma, psoriasis, bullous disease, atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, and melanoma. These diseases affect millions of individuals globally and are a serious public health concern. However, the pathogenesis of skin diseases is not fully understood, and treatments are not optimal. Yes-associated protein (YAP) is a transcriptional coactivator that plays a role in the regulation of gene transcription and signal transduction. Aims:To study the role of Yes-associated protein in skin diseases. Materials and Methods:The present review summarizes recent advances in our understanding of the role of YAP in skin diseases, current treatments that target YAP, and potential avenues for novel therapies.Results: Abnormal YAP expression has been implicated in occurrence and development of dermatosis. YAP regulates the cell homeostasis, proliferation, differentiation, apoptosis, angiopoiesis, and epithelial-to-mesenchymal transition, among other processes. As well as, it serves as a potential target in many biological processes for treating dermatosis. Conclusions:The effects of YAP on the skin are complex and require multidimensional investigational approaches. YAP functions as an oncoprotein that can promote the occurrence and development of cancer, but there is currently limited information on the therapeutic potential of YAP inhibition for cancer treatment. Additional studies are also needed to clarify the role of YAP in the development and maturation of dermal fibroblasts; skin barrier function, homeostasis, aging, and melanin production; and dermatosis.

show abstract

Topical GDF11 accelerates skin wound healing in both type 1 and 2 diabetic mouse models

Cited by 14 publications

References 18 publications

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Peptide RL‐QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds

Recent advances in the role of Yes‐associated protein in dermatosis

Contact Info

Product

Resources

About